Co-infections in people with COVID-19: a systematic review and meta-analysis

Louise Lansbury, Benjamin Lim, Vadsala Baskaran, Wei Shen Lim, Louise Lansbury, Benjamin Lim, Vadsala Baskaran, Wei Shen Lim

Abstract

Objectives: In previous influenza pandemics, bacterial co-infections have been a major cause of mortality. We aimed to evaluate the burden of co-infections in patients with COVID-19.

Methods: We systematically searched Embase, Medline, Cochrane Library, LILACS and CINAHL for eligible studies published from 1 January 2020 to 17 April 2020. We included patients of all ages, in all settings. The main outcome was the proportion of patients with a bacterial, fungal or viral co-infection. .

Results: Thirty studies including 3834 patients were included. Overall, 7% of hospitalised COVID-19 patients had a bacterial co-infection (95% CI 3-12%, n=2183, I2=92·2%). A higher proportion of ICU patients had bacterial co-infections than patients in mixed ward/ICU settings (14%, 95% CI 5-26, I2=74·7% versus 4%, 95% CI 1-9, I2= 91·7%). The commonest bacteria were Mycoplasma pneumonia, Pseudomonas aeruginosa and Haemophilus influenzae. The pooled proportion with a viral co-infection was 3% (95% CI 1-6, n=1014, I2=62·3%), with Respiratory Syncytial Virus and influenza A the commonest. Three studies reported fungal co-infections.

Conclusions: A low proportion of COVID-19 patients have a bacterial co-infection; less than in previous influenza pandemics. These findings do not support the routine use of antibiotics in the management of confirmed COVID-19 infection.

Keywords: COVID-19; Coinfection; Coronavirus; Meta-Analysis.

Conflict of interest statement

Declaration of Competing Interest LL, BL and VB declare no competing interests. WSL's institution has received unrestricted investigated-initiated research funding from Pfizer for an unrelated pneumonia cohort study in which he is the Chief Investigator.

Copyright © 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Figures

Figure 1
Figure 1
PRISMA flow diagram for study selection
Figure 2
Figure 2
Forest plot of proportion of COVID-19 patients with bacterial co-infections. Subgroup analysis for ICU versus mixed ward/ICU settings.
Figure 3
Figure 3
Forest plot of proportion of hospitalised COVID-19 patients with viral co-infections. Subgroup analysis for ICU versus mixed ward/ICU settings
Figure 4
Figure 4
Bacterial pathogens detected in COVID-19 patients, as a proportion (%) of the total number of detections (n=27) Key: M pneumoniae - Mycoplasma pneumoniae; P aeruginosa – Pseudomonas aeruginosa; H influenzae – Haemophilus influenzae; K pneumoniae – Klebsiella pneumoniae, A baumannii – Acinetobacter baumannii, S marcescens - Serratia marcescens, MRSA – Methicillin-resistant Staphylococcus aureus; E faecium – Enterococcus faecium.
Figure 5
Figure 5
Viral pathogens as a proportion (%) of the total number of viral detections (n=71). Key: RSV – Respiratory Syncytial Virus, hMPV – human Metapneumovirus, EBV – Epstein-Barr Virus, CMV - Cytomegalovirus.

References

    1. World Health Organization. Coronavirus Disease (COVID-19) pandemicAvailable from: . Accessed 13 May 2020
    1. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565–574.
    1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–733.
    1. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708–1720. doi: 10.1056/NEJMoa2002032.
    1. Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Mar 13 doi: 10.1001/jamainternmed.2020.0994.
    1. Feng Y, Ling Y, Bai T, Xie Y, Huang J, Li J. COVID-19 with Different Severity: A Multi-center Study of Clinical Features. Am J Respir Crit Care Med. 2020
    1. Joseph C, Togawa Y, Shindo N. Bacterial and viral infections associated with influenza. Influenza Other Respir Viruses. 2013;7(Suppl 2):105–113.
    1. Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, Al-Rabiah FA, Al-Hajjar S, Al-Barrak A. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect Dis. 2013;13(9):752–761.
    1. Zahariadis G, Gooley TA, Ryall P, Hutchinson C, Latchford MI, Fearon MA. Risk of ruling out severe acute respiratory syndrome by ruling in another diagnosis: variable incidence of atypical bacteria coinfection based on diagnostic assays. Can Resp J. 2006;13(1):17–22.
    1. Wang Z, Yang B, Li Q, Wen L, Zhang R. Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China. Clin Infect Dis. 2020. Mar 16 doi: 10.1093/cid/ciaa272. pii: ciaa272[Epub ahead of print]
    1. Du RH, Liu LM, Yin W, Wang W, Guan LL, Yuan ML. Hospitalization and Critical Care of 109 Decedents with COVID-19 Pneumonia in Wuhan. China. 2020 Apr 7 doi: 10.1513/AnnalsATS.202003-225OC.
    1. Wan S, Xiang Y, Fang W, Zheng Y, Li B, Hu Y. Clinical Features and Treatment of COVID-19 Patients in Northeast Chongqing. J Med Virol. 2020 Mar 21 doi: 10.1002/jmv.25783. [Epub ahead of print]
    1. Xia W, Shao J, Guo Y, Peng X, Li Z, Hu D. Clinical and CT features in pediatric patients with COVID-19 infection: Different points from adults. Pediatr Pulmonol. May 2020;55(5):1169–1174. doi: 10.1002/ppul.24718.
    1. World Health Organization. Antimicrobial resistance factsheet 2018Available from: . Accessed 13 May 2020
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.
    1. Wells G, Shea B, O'Connell D, Peterson J, V Welch, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analysesAvailable from: . Accessed 13 May 2020
    1. Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.
    1. Lansbury L, Lim B, Baskaran V, Lim WS. Co-infections in people with COVID-19: a systematic review and meta-analysis. PROSPERO. 2020 CRD42020178398 2020 Available from.
    1. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020;382(19):1787–1799. doi: 10.1056/NEJMoa2001282.
    1. Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX, Chong M. Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. JAMA. 2020 Mar 19 doi: 10.1001/jama.2020.4326. [Epub ahead of print]
    1. Barrasa H, Rello J, Tejada S, Martin A, Balziskueta G, Vinuesa C. SARS-Cov-2 in Spanish Intensive Care: Early Experience with 15-day Survival In Vitoria. Anaesth Crit Care Pain Med. 2020 Apr 9 doi: 10.1016/j.accpm.2020.04.001. pii: S2352-5568(20)30064-3[Epub ahead of print]
    1. Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK. Covid-19 in Critically Ill Patients in the Seattle Region - Case Series. N Engl J Med. 2020 Mar 30 doi: 10.1056/NEJMoa2004500. [Epub ahead of print]
    1. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513.
    1. Ding Q, Lu P, Fan Y, Xia Y, Liu M. The clinical characteristics of pneumonia patients coinfected with 2019 novel coronavirus and influenza virus in Wuhan, China. J Med Virol. 2020 Mar 20 doi: 10.1002/jmv.25781. [Epub ahead of print]
    1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China. 2020;395(10223):497–506.
    1. Lian J, Jin X, Hao S, Cai H, Zhang S, Zheng L. Analysis of Epidemiological and Clinical features in older patients with Corona Virus Disease 2019 (COVID-19) out of Wuhan. Clin Infect Dis. 2020 Mar 25 doi: 10.1093/cid/ciaa242. pii: ciaa242[Epub ahead of print]
    1. Lin D, Liu L, Zhang M, Hu Y, Yang Q, Guo J. Co-infections of SARS-CoV-2 with multiple common respiratory pathogens in infected patients. Sci China Life Sci. Apr 2020;63(4):606–609.
    1. Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020;63(3):364–374.
    1. Mo P, Xing Y, Xiao Y, Deng L, Zhao Q, Wang H. Clinical characteristics of refractory COVID-19 pneumonia in Wuhan. China. Clin Infect Dis. Mar 16 2020 doi: 10.1093/cid/ciaa270. pii: ciaa270[Epub ahead of print]
    1. Pongpirul WA, Mott JA, Woodring JV, Uyeki TM, MacArthur JR, Vachiraphan A. Clinical Characteristics of Patients Hospitalized with Coronavirus Disease, Thailand. Emerg Infect Dis. 2020;26(7) doi: 10.3201/eid2607.200598. [Epub ahead of print]
    1. Tagarro A, Epalza C, Santos M, Sanz-Santaeufemia FJ, Otheo E, Moraleda C. Screening and Severity of Coronavirus Disease 2019 (COVID-19) in Children in Madrid, Spain. JAMA Pediatr. Apr 8 2020 doi: 10.1001/jamapediatrics.2020.1346. [Epub ahead of print]
    1. Wang L, He W, Yu X, Hu D, Bao M, Liu H. Coronavirus Disease 2019 in elderly patients: characteristics and prognostic factors based on 4-week follow-up. J Infect. Mar 30 2020 doi: 10.1016/j.jinf.2020.03.019. pii: S0163-4453(20)30146-8[Epub ahead of print]
    1. Wang Y, Liu Y, Liu L, Wang X, Luo N, Li L. Clinical Outcomes in 55 Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Who Were Asymptomatic at Hospital Admission in Shenzhen, China. J Infect Dis. May 11 2020;221(11):1770–1774.
    1. Wu J, Liu J, Zhao X, Liu C, Wang W, Wang D. Clinical Characteristics of Imported Cases of COVID-19 in Jiangsu Province: A Multicenter Descriptive Study. Clin Infect Dis. Feb 29 2020 doi: 10.1093/cid/ciaa199. pii: ciaa199[Epub ahead of print]
    1. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. May 2020;8(5):475–481.
    1. Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J. Epidemiologic Features and Clinical Course of Patients Infected with SARS-CoV-2 in Singapore. JAMA. Mar 3 2020 doi: 10.1001/jama.2020.3204. [Epub ahead of print]
    1. Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. Feb 19 2020 doi: 10.1111/all.14238. [Epub ahead of print]
    1. Zhao D, Yao F, Wang L, Zheng L, Gao Y, Ye J. A comparative study on the clinical features of COVID-19 pneumonia to other pneumonias. Clin Infect Dis. Mar 12 2020 doi: 10.1093/cid/ciaa247. pii: ciaa247[Epub ahead of print]
    1. Zheng F, Liao C, Fan QH, Chen HB, Zhao XG, Xie ZG. Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China. Curr Med Sci. 2020;40(2):275–280.
    1. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062.
    1. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(5):846–848.
    1. Kim D, Quinn J, Pinsky B, Shah NH, Brown I. Rates of Co-infection Between SARS-CoV-2 and Other Respiratory Pathogens. JAMA. Apr 15 2020 doi: 10.1001/jama.2020.6266. [Epub ahead of print]
    1. MacIntyre CR, Chughtai AA, Barnes M, Ridda I, Seale H, Toms R. The role of pneumonia and secondary bacterial infection in fatal and serious outcomes of pandemic influenza a(H1N1)pdm09. BMC Infect Dis. 2018;18(1):637.
    1. Chertow DS, Memoli MJ. Bacterial coinfection in influenza: a grand rounds review. JAMA. 2013;309(3):275–282.
    1. Klein EY, Monteforte B, Gupta A, Jiang W, May L, Hsieh YH. The frequency of influenza and bacterial coinfection: a systematic review and meta-analysis. Influenza Other Respir Viruses. 2016;10(5):394–403.
    1. Arabi YM, Balkhy HH, Hayden FG, Bouchama A, Luke T, Baillie JK. Middle East Respiratory Syndrome. N Engl J Med. 2017;376(6):584–594.
    1. Hwang DM, Chamberlain DW, Poutanen SM, Low DE, Asa SL, Butany J. Pulmonary pathology of severe acute respiratory syndrome in Toronto. Mod Pathol. 2005;18(1):1–10.
    1. Sobieszczanska BM, Kasprzykowska U, Duda-Madej A, Secewicz A, Marciniak J, Gosciniak G. Relevance of serology for Mycoplasma pneumoniae infection among children with persistent cough. Adv Clin Exp Med. 2014;23(2):185–190.
    1. Jones RN. Microbial etiologies of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. Clin Infect Dis. 2010;51(Suppl 1):S81–S87.
    1. Alanio A, Dellière S, Fodil S, Bretagne S, B.M. High Prevalence of Putative Invasive Pulmonary Aspergillosis in Critically Ill COVID-19 Patients (April 14, 2020) Available from: SRN: or 10.2139/ssrn.3575581. Accessed 13 May 2020
    1. Blaize M, Mayaux J, Nabet C, Lampros A, Marcelin AG, Thellier M. Fatal Invasive Aspergillosis and Coronavirus Disease in an Immunocompetent Patient. Emerg Infect Dis. Apr 28 2020;26(7) doi: 10.3201/eid2607.201603. [Epub ahead of print]
    1. Koehler P, Cornely OA, Bottiger BW, Dusse F, Eichenauer DA, Fuchs F. COVID-19 Associated Pulmonary Aspergillosis. Mycoses. Apr 27 2020 doi: 10.1111/myc.13096. [Epub ahead of print]
    1. Lescure FX, Bouadma L, Nguyen D, Parisey M, Wicky PH, Behillil S. Clinical and virological data of the first cases of COVID-19 in Europe: a case series. Lancet Infect Dis. Mar 27 2020 doi: 10.1016/S1473-3099(20)30200-0. pii: S1473-3099(20)30200-0[Epub ahead of print]
    1. van Arkel ALE, Rijpstra TA, Belderbos HNA, van Wijngaarden P, Verweij PE, Bentvelsen RG. COVID-19 Associated Pulmonary Aspergillosis. Am J Respir Crit Care Med. 2020 May 12 doi: 10.1164/rccm.202004-1038LE. [Epub ahead of print]
    1. Koehler P, Bassetti M, Kochanek M, Shimabukuro-Vornhagen A, Cornely OA. Intensive care management of influenza-associated pulmonary aspergillosis. Clin Microbiol Infect. 2019;25(12):1501–1509.
    1. Schauwvlieghe A, Rijnders BJA, Philips N, Verwijs R, Vanderbeke L, Van Tienen C. Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study. Lancet Respir Med. 2018;6(10):782–792.
    1. Hope WW, Walsh TJ, Denning DW. Laboratory diagnosis of invasive aspergillosis. Lancet Infect Dis. 2005;5(10):609–622.
    1. D'Haese J, Theunissen K, Vermeulen E, Schoemans H, De Vlieger G, Lammertijn L. Detection of galactomannan in bronchoalveolar lavage fluid samples of patients at risk for invasive pulmonary aspergillosis: analytical and clinical validity. J Clin Microbiol. 2012;50(4):1258–1263.
    1. Meersseman W, Lagrou K, Maertens J, Wilmer A, Hermans G, Vanderschueren S. Galactomannan in bronchoalveolar lavage fluid: a tool for diagnosing aspergillosis in intensive care unit patients. Am J Respir Crit Care Med. 2008;177(1):27–34.
    1. Patterson TF, Thompson GR, 3rd Denning DW, Fishman JA, Hadley S, Herbrecht R. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1–e60.
    1. Zhou W, Li H, Zhang Y, Huang M, He Q, Li P. Diagnostic Value of Galactomannan Antigen Test in Serum and Bronchoalveolar Lavage Fluid Samples from Patients with Nonneutropenic Invasive Pulmonary Aspergillosis. J Clin Microbiol. 2017;55(7):2153–2161.
    1. Wahidi MM, Lamb C, Murgu S, Musani A, Shojaee S, Sachdeva A. American Association for Bronchology and Interventional Pulmonology (AABIP) Statement on the Use of Bronchoscopy and Respiratory Specimen Collection in Patients with Suspected or Confirmed COVID-19 Infection. J Bronchology Interv Pulmonol. Mar 18 2020 doi: 10.1097/LBR.0000000000000681. [Epub ahead of print]
    1. Verweij PE, Gangneux J-P, Bassetti M, Brüggemann RJM, Cornely OA, Koehler P. Diagnosing COVID-19-associated pulmonary aspergillosis. Lancet Microbe. May 08 2020 doi: 10.1016/S2666-5247(20)30027-6.
    1. Shu YL, Fang LQ, de Vlas SJ, Gao Y, Richardus JH, Cao WC. Dual seasonal patterns for influenza, China. Emerg Infect Dis. 2010;16(4):725–726.
    1. World Health Organization. Coronavirus disease 2019 (COVID-19) Situation Report – 99 Available from:. Accessed 13 May 2020
    1. Hunter JP, Saratzis A, Sutton AJ, Boucher RH, Sayers RD, Bown MJ. In meta-analyses of proportion studies, funnel plots were found to be an inaccurate method of assessing publication bias. J Clin Epidemiol. 2014;67(8):897–903.
    1. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. Apr 22 2020 doi: 10.1001/jama.2020.6775. [Epub ahead of print]

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